"Ann Arbor, MI - New laboratory research suggests that the COX-2 inhibitor celecoxib (Celebrex, Pfizer), might impede the action of "baby" aspirin [1]. Dr Gilad Rimon (University of Michigan, Ann Arbor) and colleagues found evidence that this was the case in a dog model and say that "it will be important to determine" whether the same is true in humans.

The report was published online December 1, 2009 in the Proceedings of the National Academy of Medicine.

Celecoxib is the only COX-2 inhibitor to have remained on the market in the US, and doctors who recommend this painkiller often coprescribe a daily low dose of 81 mg of aspirin (known as a "baby" dose) to counteract any possible prothrombotic effects of the coxib, while minimizing potential gastrointestinal toxicity of the aspirin.

Senior author of the new work, Dr William L Smith (University of Michigan, Ann Arbor), explained to heartwire that previous studies in humans have shown that celecoxib does not interfere with the effect of a standard dose of aspirin (325 mg), but any potential interaction of celecoxib with the lower dose has not been examined.

Stagger dosing to avoid any potential problems

First, Smith explained that he and his colleagues looked in vitro at celecoxib and found that it binds to one of two available sites on the COX-1 enzyme. "This surprised us," he commented. "It appears to interfere with the ability of some other drugs to affect COX-1, most notably aspirin."

Second, in beagles, they administered the dog-equivalent of a baby dose of aspirin in humans and then gave some of the animals the equivalent of 100 mg of celecoxib twice daily in addition. "Celecoxib plus aspirin interfered with the normal effect of low-dose aspirin on platelets," he notes.

Smith says this observation obviously requires confirmation in humans, but in the meantime he suggests "getting around the problem" by patients taking the low-dose aspirin at least 15 to 30 minutes before the celecoxib is taken, "because

It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

"Good research is good for medicine. The only thing more important than good research is ethical research. The February 16th issue of the New England Journal of Medicine (NEJM) had a research paper on vitamin D and colon cancer. Was it good research? Was it ethical research? At stake are the lives of 36,000 older American women who agreed to participate in the Women's Health Initiative. "

This IRX-2 strategy uses perilymphatic local administration along with contrasuppression with low-dose cyclophosphamide and indomethacin and with zinc replacement therapy (as an immunorestorative). The data presented herein demonstrate that H&N SCC can respond very well to immunotherapy: there was a response rate of 100% in this series of 15 patients, with clinical reduction in tumor (1 complete response, 7 partial responses, and 7 minor responses) and histological evidence of tumor regression of 42%. Overall, the average combined estimated tumor reduction exceeded 70%. Also, patients with oral cancer noted marked analgesic and hemostatic effects from this therapy, with healing of oral lesions.

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It is important to note that adjuvant chemotherapy is not used at INCAN. Many studies23 indicate that treatment with fluorouracil and cisplatin, the combination most in use, is effective for reducing tumors in the majority of patients; however, with no meaningful impact on survival, their routine use in the United States has recently been questioned.24-25 The expense, toxic effects, and lack of effectiveness of both drugs has made their use in other less affluent countries unwarranted. The current data on the use of IRX-2 in this and other protocols8-10 hint at improved survival, and a phase 3 randomized controlled study comparing this protocol with chemotherapy arm is to be initiat